Bleomycin, macromomycin, and hematoporphyrin are potent tumoricidal agents that have the unusual property of preferentially localizing on or within malignant cells. Based on work that we have carried out in our own laboratories, together with that done by others, it is clear that bleomycin and macromomycin can evoke an immune response, either humoral, cellular, or both depending upon the properties of the carrier species and the route and mode of immunization. Based on methodology that we already have developed, it should be possible to make hematoporphyrin immunogenic. The tumor localizing and cytotoxic properties of these three drugs, each exerted by a different mechanism, suggest that if a sensitized tumor-bearing animal were given the derivatized drug either systemically or intralesionally, that the ensuing immune response, directed against the drug, the carrier, or the drug-carrier complex, would also be cytotoxic to the tumor cells to which the drug-carrier complex was bound. The specific aims of this proposal are three-fold: 1) To chemically modify three tumoricidal drugs that have tumor localizing properties; bleomycin, macromomycin, and hematoporphyrin by linking them to either a lipid-conjugated protein carrier molecule or a lipid so that they become capable of evoking a drug or carrier directed, cell-mediated immune response and to study this by in vivo and in vitro methods. 2) To develop immunotherapeutic models employing these chemically modified drugs. 3) To study the binding affinity that these drugs and their derivatives have for the surface membranes of malignant cells and the possible relationship that this has to their therapeutic effect. In this immunotherapy model that we propose, the cell mediated response will be directed against either the unmodified or the chemically modified drug, carrier, or drug-carrier complex localized on the surface membranes of malignant cells. It does not depend upon the drug retaining its anti-neoplastic activity although this would be an added advantage.